Decomposing heritability and genetic covariance by direct and indirect effect paths.
Estimation of heritability and genetic covariance is crucial for quantifying and understanding complex trait genetic architecture and is employed in almost all recent genome-wide association studies (GWAS). However, many existing approaches for heritability estimation and almost all methods for esti...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-01-01
|
| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1010620 |
| _version_ | 1797833051784347648 |
|---|---|
| author | Jie Song Yiqing Zou Yuchang Wu Jiacheng Miao Ze Yu Jason M Fletcher Qiongshi Lu |
| author_facet | Jie Song Yiqing Zou Yuchang Wu Jiacheng Miao Ze Yu Jason M Fletcher Qiongshi Lu |
| author_sort | Jie Song |
| collection | DOAJ |
| description | Estimation of heritability and genetic covariance is crucial for quantifying and understanding complex trait genetic architecture and is employed in almost all recent genome-wide association studies (GWAS). However, many existing approaches for heritability estimation and almost all methods for estimating genetic correlation ignore the presence of indirect genetic effects, i.e., genotype-phenotype associations confounded by the parental genome and family environment, and may thus lead to incorrect interpretation especially for human sociobehavioral phenotypes. In this work, we introduce a statistical framework to decompose heritability and genetic covariance into multiple components representing direct and indirect effect paths. Applied to five traits in UK Biobank, we found substantial involvement of indirect genetic components in shared genetic architecture across traits. These results demonstrate the effectiveness of our approach and highlight the importance of accounting for indirect effects in variance component analysis of complex traits. |
| first_indexed | 2024-04-09T14:18:36Z |
| format | Article |
| id | doaj.art-88c1fcf0c59a44f9b8ca9f49c40db59f |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-04-09T14:18:36Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-88c1fcf0c59a44f9b8ca9f49c40db59f2023-05-05T05:30:47ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042023-01-01191e101062010.1371/journal.pgen.1010620Decomposing heritability and genetic covariance by direct and indirect effect paths.Jie SongYiqing ZouYuchang WuJiacheng MiaoZe YuJason M FletcherQiongshi LuEstimation of heritability and genetic covariance is crucial for quantifying and understanding complex trait genetic architecture and is employed in almost all recent genome-wide association studies (GWAS). However, many existing approaches for heritability estimation and almost all methods for estimating genetic correlation ignore the presence of indirect genetic effects, i.e., genotype-phenotype associations confounded by the parental genome and family environment, and may thus lead to incorrect interpretation especially for human sociobehavioral phenotypes. In this work, we introduce a statistical framework to decompose heritability and genetic covariance into multiple components representing direct and indirect effect paths. Applied to five traits in UK Biobank, we found substantial involvement of indirect genetic components in shared genetic architecture across traits. These results demonstrate the effectiveness of our approach and highlight the importance of accounting for indirect effects in variance component analysis of complex traits.https://doi.org/10.1371/journal.pgen.1010620 |
| spellingShingle | Jie Song Yiqing Zou Yuchang Wu Jiacheng Miao Ze Yu Jason M Fletcher Qiongshi Lu Decomposing heritability and genetic covariance by direct and indirect effect paths. PLoS Genetics |
| title | Decomposing heritability and genetic covariance by direct and indirect effect paths. |
| title_full | Decomposing heritability and genetic covariance by direct and indirect effect paths. |
| title_fullStr | Decomposing heritability and genetic covariance by direct and indirect effect paths. |
| title_full_unstemmed | Decomposing heritability and genetic covariance by direct and indirect effect paths. |
| title_short | Decomposing heritability and genetic covariance by direct and indirect effect paths. |
| title_sort | decomposing heritability and genetic covariance by direct and indirect effect paths |
| url | https://doi.org/10.1371/journal.pgen.1010620 |
| work_keys_str_mv | AT jiesong decomposingheritabilityandgeneticcovariancebydirectandindirecteffectpaths AT yiqingzou decomposingheritabilityandgeneticcovariancebydirectandindirecteffectpaths AT yuchangwu decomposingheritabilityandgeneticcovariancebydirectandindirecteffectpaths AT jiachengmiao decomposingheritabilityandgeneticcovariancebydirectandindirecteffectpaths AT zeyu decomposingheritabilityandgeneticcovariancebydirectandindirecteffectpaths AT jasonmfletcher decomposingheritabilityandgeneticcovariancebydirectandindirecteffectpaths AT qiongshilu decomposingheritabilityandgeneticcovariancebydirectandindirecteffectpaths |